FR2556717A1 - NOVEL 3-BENZYLIDENE CAMPHRE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS PROTECTIVE AGENTS AGAINST UV RAYS AND AS MEDICAMENTS - Google Patents

Abstract

DERIVATIVES OF 3-BENZYLIDENE CAMPHOR OF FORMULA: (CF DRAWING IN BOPI) IN WHICH R DESIGNATES A HYDROGEN ATOM, A RADICAL METHYL OR ETHYL, R DESIGNates A HYDROGEN ATOM, A RADICAL METHYL OR ETHYL, R AND R CANNOT BE SIMULTANEOUSLY DESIGNATE A HYDROGEN ATOM, R DESIGNATES A -COOR, -CONHR, -COOM, -CHO, -CH (OR) OR -CHOR, R BEING A RADICAL ALKYL, ALKENYL, CYCLOALKYL OR ARALKYL CONTAINING A MAXIMUM OF 20 ATOMS OF CARBON, POSSIBLY SUBSTITUTED BY HYDROXY, ALCOXY, AMINE OR QUATERNARY AMMONIUM, M DESIGNING AN ATOM OF HYDROGEN, AN ALKALINE METAL OR AN N (R) GROUP, R BEING A HYDROGEN ATOM OR A HYDROGEN ATOM OR A HYDROGEN ALKYL OR HYDROGEN ATOM , R DESIGNING H, ALKYL, CYCLOALKYL OR ARALKYL CONTAINING A MAXIMUM OF 20 CARBON ATOMS. APPLICATION IN COSMETICS FOR PROTECTION AGAINST UV RAYS. THERAPEUTIC APPLICATION FOR THE TREATMENT OF DERMATOLOGICAL AND RHEUMATISMAL AFFECTIONS; ANTITUMOR ACTION.

Description

Novel 3-benzylidene camphor derivatives, process for their preparation and

  their use as agents for protection against UV radiation and in

as medicines.

  The present invention relates to novel compounds derived from 3-benzylidene camphor, and to their process of preparation and their use for protection against ultraviolet radiation in the

  cosmetic field and as medicaments.

  Light radiation with wavelengths between 280 and 400 nm is known to allow the browning of the human epidermis and the wavelength rays between 280 and 320 nm known under the name UV-B also cause erythema and skin burns

  which can hinder the development of the tan.

  The use of active compounds in the long-term zone is already known.

  above 280-320 nm. U.S. Patent 3,781,417 is described by way of

  1S of UV-B absorber the 3- (4'-methylbenzylidene) camphor of which the maximum of

  sorption is at 297 nm. This compound has good solubility in

  oils, but is insoluble in water.

  Other benzylidene camphor derivatives are also known for

  possess absorption properties in the wavelength zone 280-

  320 rm. These are benzylidenecamphor derivatives containing a quaternary ammonium radical on the benzene ring in the para position relative to the bornylidene radical according to French Patent No. 2 199 971, sulfonated benzylidene camphor derivatives on the methyl radical at position 10 of the camphor or in position 3 'or 4' on the benzene ring according to French Patent Nos. 2 282 426 and 2 236 515, p-methylbenzylidene camphor derivatives substituted on the p-methyl group according to French patents 2 383 904, 2 402 647

and 2,421,878.

  It is also known that the constituents used in the preparations

  cosmetics and in particular certain dyes of dye compositions

  colored hairspray, shampoos, styling lotions, make-up products such as tinted creams, varnishes

  nails, lipstick sticks, do not always have a stabi-

  sufficient light and that they degrade under the action of radia-

light.

  It has been found desirable to broaden the group of compounds capable of absorbing UV-B rays, having good solubility in the usual cosmetic solvents and carriers and protecting both the human epidermis and the various products sensitive to these radiations by application. on the skin or incorporation into products, preparations and compositions sensitive to these radiations.

  The Applicant has discovered that certain derivatives of 3-beuzylidene cam-

  were surprisingly good filtering properties with respect to UV-B rays, were perfectly soluble in the usual cosmetic solvents and had good thermal stability and

excellent photochemical stability.

  The subject of the present invention is therefore new 3-benzyl derivatives.

  camphor lidene having the formula R (I)

I

f

R '-

  in which R denotes a hydrogen atom, a methyl or ethyl radical, R 'denotes a hydrogen atom, a methyl or ethyl radical, R and R' can not simultaneously designate a hydrogen atom, R1 denotes a group - COOR 2, -CONHR 2, -COO, -CHO, -Ct (OR 4) 2 or

-CH20R4,

  R2 being an alkyl, alkenyl, cycloalkyl or aralkyl radical containing at most 20 carbon atoms, optionally substituted by hydroxyl, alkoxy, amine or quaternary ammonium groups, M denoting a hydrogen atom, an alkali metal or a P (R 3) group; ) 4, R3 being a hydrogen atom or a C1-C4 alkyl or hydroxyalkyl radical, R4 denotes a hydrogen atom or an alkyl, cyclolyl or

  aralkyl containing at most 20 carbon atoms.

  The preferred compounds are those in which R and R 'do not denote

  simultaneously a methyl or ethyl radical.

  Among the preferred radicals R 2 and R 4 include methyl, ethyl, propyl, butyl, hexyl, 2-ethylhexyl. Depending on the nature of the substituent R 1, the compounds of formula (I) according to

  the invention are water-soluble or fat-soluble. When R1 designates a group

  -COOR2 or -CONHR2, they are soluble in oils; when R1 denotes -C0, M being different from a hydrogen atom, they are soluble in

the water.

  The present invention also relates to a preparation process

  new compounds of formula (I).

  The compounds of formula (I) are obtained according to the three reaction schemes

  1) R = H and R '= methyl or ethyl bromination hydrolyzed CH R Br- / N \ R' P- 4 4condensation oxidation + (alkyl-O) 2PCH2 CORW2

Wittig-Horner

CH

HO RI'0

+ (alkyl-O) 2 P-OH x Rt

C02R2

  This process is a succession of 4 conventional syntheses, the first being a bromination generally carried out in an inert solvent medium using a brominating agent such as N-bromosuccinimide, at the reflux temperature of the mixture. This bromination is followed by hydrolysis with sodium hydroxide, at a temperature of about 100 C, of the brominated derivative obtained. The third step consists of an oxidation of a secondary alcohol to a ketone using, for example, a mixture of potassium dichromate and concentrated sulfuric acid. The last step is a reaction known as WITTIG condensation

  that can be defined as the condensation of a triarylphosphorus salt

  nium on a carbonyl function to lead to a group or an unsaturated compound. This condensation is carried out in a polar solvent such as tetrahydrofuran in the presence of a strong base such as sodium hydride; in general, in the case where the cation associated with the base is sodium, very small amounts of pentaoxa-l, 4,7,10,13 cyclopentadecane are also added.

  Its function is to increase the basicity of the medium. In the process of

  a phosphonate (alkyl-O) 2 -P-CH 2 CoO 2 R 2 is used instead of a phosphonium salt, alkyl being preferably methyl or ethyl; it is therefore

  a modified WITTIG condensation (WITTIG-HORNER reaction).

  20) R = methyl or ethyl and R '= H condensation

+ (alkyl-O) 2 -O - -O-alkyl -

  ## STR3 ## wherein R 2 + oxy-RORNER R 2 is oxidation R 2 + (alkyl-O) 2 P-OH-, t / A

0 CH 20H

alkyl R 0 condensation

+ (alkyl-O) 2CH 2 COO 2 R 2 -

Wittig-Horner

H = CHC00R2

\ H

  The first and fourth steps are condensations of WITTIG-

  HORNER using a phosphonate in which alkyl is preferably

  methyl or ethyl, carried out under the operating conditions defined below.

above in 1).

  The second and third steps using conventional methods which are the reduction of a carbalkoxy group using a strong reducing agent such as aluminum hydride and lithium in an inert solvent medium to obtain the primary alcohol and the oxidation of this alcohol function according to

  aldehyde by action for example pyridinium chlorochromate.

  3) R and R 'simultaneously denote methyl or ethyl. 1- (2'-oxo-3'-bornbornidene) -1- (4'-formylphenyl) ethane or 1,12'-oxo-3-bornylidane may be reacted. 1- (4'-Formylphenyl) propane obtained in the 3rd step of Reaction Scheme 2) above, with an organomagnesium such as

  methyl or ethyl magnesium bromide or iodide to convert aldehyde

  hyde in secondary alcohol, which is subjected to an oxidation to obtain the ketone, which one finally condenses with a phosphonate according to the reaction of

  Wittig-Horner to obtain the desired compounds.

  In the three reaction schemes above, the compounds (I) in which R 1 is -COO 2 R 2 are obtained. By saponification, these compounds are converted to the corresponding acids in which R 1 denotes -COOR, which can be salified with an alkaline base or an amine to give compounds (I) where R 1 denotes C0t M, M being an alkaline ion or a group

J (R3) 4-

  By a known process, it is also possible to convert the acid into chloride

  of acid by the action of phosphorus trichloride, the acid chloride reacts with

2556 7 17

  then with an amine to form the corresponding amide of formula (I)

wherein R1 is -CONHR2.

  The esters of formula (I) in which R 1 is -COO 2 can be reduced to form the alcohols, that is to say the compounds of formula (I) in which R 1 denotes -CH 2 OH. By oxidation of alcohols, we obtain the

corresponding aldehydes.

  Acetals of formula (I) in which R 1 denotes -CH (OR 4) 2 are derived from aldehydes by addition thereto of alkanols, cycloalkanols or aralkyl alcohols in an acidic medium. They can also be obtained by addition of aldehydes to the compound of formula (I) in which R

denotes -CH2OH in an acid medium.

  The ethers of formula (1) in which R 1 is -CH 2 O 4 R 4 are obtained from the corresponding alcohols, by the action of an alkyl halide,

cycloalkyl or aralkyl.

  The compounds according to the invention of formula (I) are illustrated by the following nonlimiting examples

Example 1

  Preparation of a compound of general formula (Ij in which R = H, R 'CH3 and R1OC2 5 H3C "

02C2H5

'C02ó2H5

  1) Preparation of 4'-bromoethyl-3-benzylidenecamphor of formula: ## STR2 ## A solution of 34.8 g of

  4'-ethyl-3-benzylidene camphor, 25 g of N-bromosuccinimide and 0.300 g of azo-

  bis-isobutyronitrile in 500 cm3 of CC14. Let's go back to temperature

  ambient and filtered the succinimide. The organic phase is washed with bicarbonate

  sodium bonate then with water and the solvent is evaporated. We obtain 37 g of

  4'-bromoethyl-3-benzylidene camphor.

  2) Preparation of 4'-hydroxyethyl-3-benzylidenecamphor of formula:

HOH

H3

  A suspension of 30 g of 4'-bromine is heated at 100 ° C. for 6 hours.

  ethyl-3-benzylidenecamphor obtained above in 200 cm3 of 3N sodium hydroxide. At the end of the reaction, the product is extracted with ether. The organic phase is washed with water and then dried over sodium sulphate. After evaporation, 21 g of

  4'-hydroxyethyl-3-benzylidene camphor.

  3) Preparation of 4'-acetyl-3-benzylidenecamphor of formula:

CH3

  14 g of potassium dichromate are dissolved in 12 g of sulfuric acid

  concentrated and 75 g of ice. 20 g of 4'-hydroxyethyl-3-benzyl are added

Dene-camphor.

  It is heated at 80 ° C. for 15 minutes and then allowed to cool. We ex-

  ether, the organic phase is washed with water, dried over sodium sulphate and the solvent is evaporated off under reduced pressure. The product is purified

  by chromatography on silica gel (elution with dichloromethane). We ob-

  holds 8.2 g of 4'-acetyl-3-benzylidenecamphor.

  4) Condensation of 4'-acetyl-3-benzylidenecamphor with phosphonoacetate

triethyl te.

  To a solution of 1.58 g of triethyl phosphonoacetate in 20 cm3 of anhydrous THF, 0.35 g of 50% sodium hydride in oil and 0.30 g of pentaoxa-1,4,7 are added. , 10,13-cyclopentadecane. A solution of 2 g of 4'-acetyl-3-benzylidenecamphor in 10 cm3 of anhydrous THF is introduced dropwise. It is stirred for 1 hour at room temperature. Pour the mixture

  reaction in cold water. Extracted with ether, the organic phase is washed

  than with a saturated solution of sodium bicarbonate, then with water. The solvent is evaporated and the product is purified by chromatography on silica gel (eluent: toluene-ethyl acetate 95: 5). 1.3 g of pale yellow thick liquid having the following characteristics are obtained: Elemental analysis:

C H O

  Calculated 78.41 7.95 13.64 Found 78.36 7.97 13.67> max = 315 nm <= 35800 (methanol)

IZ -HN-

  Sú Hiz:) - a _ lx _z a úHa- * x HR = J e llinbeI suep (I) aIlauD {2 alnumxo; ap 0sodmoz unp uoT :: i [daxd SZ ú aIdurox - (IoUtqL-) 000 Where u =, mue 1E = x'eUN <16'9I LC'L ZL'LL anoIli 18i'I It * L-- 8L ' LL glnvle3 o HD: hi> Tns sanbTzlsTa lwsj1 salt suep9ssod 'apT; ep 2 8G0 luellqo uo ap'TA snos aqzis uo ze eatl uO' alll uo ze tú IDH lud 9F3TPFat> uo * 1e, 1 aFST-P uo za nsa, p ú m-5 Z Z Z Z I I I I ne ne ne ne ne E E E; ú n n n u u u u u,,,,, 2 2 2 2 2 2 2 2 2 2 HC HC HC HC HC HC HC HC HC HC HC - - - - - - - - - - - - - - - - - - - xo; 2 g of acid obtained in Example 2 are added to 30 cm 3 of benzene and 1 g of phosphorus trichloride. EXAMPLE 2 It is heated under nitrogen at 50 C until the product is dissolved. After 1 hour of heating, the solvent is evaporated off under reduced pressure. The residue is redissolved in 20 cm3 of ether and added dropwise at -30 ° C. to a solution of 1 g of ethylamine in 10 cm3 of ether. The reaction mixture is cooled to room temperature. The mixture is stirred for 2 hours and then the organic phase is washed with water, dried over sodium sulphate and the solvent is evaporated off under reduced pressure. 1.5 g of product having the following characteristics are obtained: Elemental analysis:

C H N O

  Calculated 78.63 8.26 3.99 9.12 Found 78.60 8.30 3.96 9.14 N max = 318 nm; = 36,000 (ethanol)

Example 4

  Preparation of a compound of general formula (I) in which: R = -CH3, R '= Het R1 = -OC2

H3

02C2H5

  1.66 g of camphoroquinone and 3 g of 4-methoxycarbonyl-phenyl are added.

  diethyl ethylphosphonate with a suspension of 0.5 g of sodium hydride

  in 20 cm3 of tetrahydrofuran containing 0.05 g of pentaoxa-1,4,7,10,13-

  cyclopentadecane. Stir at room temperature overnight. The melange

  The reaction mixture is poured into water and the product is extracted with acetate.

  ethyl. After distillation of the solvent, the product is purified by chromatography

  silica gel (solvent: hexane + 5% ethyl acetate).

  The compound obtained is dissolved in 50 cm3 of ether. 1 g of hy-

  aluminum and lithium paste and stirred overnight at room temperature. The excess hydride is destroyed by ethyl acetate. We dilute to

  the water is extracted with ether and the organic phase is dried. After distillation

  solvent, 0.9 g of product is obtained which is redissolved in cm3 anhydrous dichloromethane. 1.9 g of pyridinium chlorochromate are added and the reaction mixture is stirred for 3 hours at room temperature. It is diluted with 50 cm 3 of ether, filtered through Celite and evaporated on

  solvent. After purification on silica gel (solvent: hexane + 2% acetonitrile)

  ethyl acetate), the product is added to a solution of 0.4 g of phosphono-

  triethyl acetate in 1 cm3 of tetrahydrofuran containing 0.1 g of hy-

  sodium chloride and 0.01 g of pentaoxa-1,4,7,10,13-cyclopentadecane. Stirred for 1 hour at room temperature and then diluted with ether. The solution is filtered through Celite and the product is purified by gel chromatography.

  silica (solvent: hexane + 2% ethyl acetate). We obtain 0.5 g of

  duit having the following characteristics: Elemental analysis:

C H O

  Calculated 78.41 7.95 13.64 Found 78.45 7.99 13.55 max = 306 nm; The present invention also relates to a cosmetic composition containing, as protection agent against UV-B rays, at least one 3-benzylidene camphor derivative of formula (I) according to the invention in a

cosmetically acceptable medium.

  The cosmetic composition according to the invention, when it is used as a composition intended to protect the human epidermis against the rays

  ultraviolet light, may be in the most common forms

  used for this type of composition. It is in particular in the form of a solution, a lotion, an emulsion such as a cream or a milk, a hydroalcoholic or alcoholic gel, a solid stick or it is packaged in

aerosol.

  It may contain the cosmetic adjuvants usually used in this type of composition, such as thickeners, softeners,

  humectants, superfatting agents, emollients, wetting agents, tensio-

  active ingredients, preservatives, anti-foams, perfumes, oils,

  waxes, dyes and / or pigments whose function is to color the

  position itself or the skin, bactericides or any other ingredient

  usually used in cosmetics.

  The compound of formula (I) is present in particular in proportions

  between 0.5 and 15% of the total weight of the compound

sition.

  As the solubilization solvent, it is possible to use a monoalcohol or a lower polyol or mixtures thereof, or an aqueous-alcoholic solution. The

  monoalcohols or polyols which are particularly preferred are ethanol, isopropanol and

  panol, propylene glycol or glycerin.

  An embodiment of the invention is an emulsion in the form of cream or protective milk additionally comprising compounds of formula (I), fatty alcohols, ethoxylated fatty alcohols, esters of fatty acids and especially triglycerides of fatty acids, fatty acids, lanolin,

  natural or synthetic oils, waxes in the presence of water.

  Another embodiment consists of lotions such as oleoalcoholic lotions based on a lower alcohol such as ethanol, or a glycol such as propylene glycol and / or a polyol such as glycerine.

  and fatty acid esters such as triglycerides of fatty acids.

  The cosmetic composition of the invention may also be a hydroalcoholic gel comprising one or more lower alcohols such as ethanol, propylene glycol or glycerol and a thickener, in the presence of water.

  The present invention also relates to the anti-cosmetic compositions

  sunscreens containing at least one compound of formula (I) which may be associated with

  other sun filters specific for UV-B radiation and / or

  UV-A and compatible with the compounds according to the invention. We can thus obtain a formulation filtering all UV-B and UV-A radiation. The present invention also relates to protective day creams containing at least one compound of formula (1) associated with at least one UV-A filter. The compounds according to the invention can be combined with UV-B filters

  consisting of liposoluble compounds or oils having

  filtering properties such as in particular the coffee oil. As

  lipophilic UV-B sunscreens, mention may be made of the derivatives of salic acid

  cyclic such as 2-ethylhexyl salicylate, homomenthyl salicylate,

  cinnamic acid derivatives such as 2-methyl p-methoxycinnamate

  hexyl, 2-ethoxyethyl p-methoxycinnamate, acid derivatives

  p-aminobenzoic compounds such as amyl p-aminobenzoate, p-dimethylamino

  2-ethylhexyl zoate, benzophenone derivatives such as 2-hydroxyhexyl

  2'-methoxybenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone, derivatives thereof

  such as 3- (4'-methylbenzylidene) camphor associated with

  with 4-isopropyldibenzoylmethane or 3-benzylidenecamphor.

  As water-soluble sunscreens filtering the UV-B rays which can also be associated with the fat-soluble or water-soluble filters of the invention provided they are compatible with the latter, mention may be made of the benzylidene camphor derivatives described in the French patents.

  Nos. 2 199 971, 2 236 515 and 2 383 904 of the applicant and more particularly

  4- (2-oxo-3-bornylidene-methyl) phenyltrimethylammonium methylsulphate

  monium, salts of 4- (2-oxo-3-bornylidenemethyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bornylidenemethyl) benzenesulphonic acid and

  2-phenylbenzimidazole-5-sulfonic acid.

2 5 5 6 7 17

  The compounds according to the invention can also be combined with

  UV-A, among which mention may be made of dibenzoylmethane derivatives.

  It is understood that the list of sunscreens used in combination with the compounds (I) according to the invention which is indicated above is not limiting. The sunscreen compositions according to the invention may be in the form of solutions, lotions, emulsions such as a cream or a milk, in the form of oils, fatty gels, hydroalcoholic or alcoholic gels or may be packaged in an aerosol in solid sticks. They may contain the aforementioned cosmetic adjuvants usually used in this type

of compositions.

  The present invention also relates to the cosmetic compositions

  or not containing at least one compound of formula (I) as a

protection against UV-B rays.

  These compositions can be constituted by capillary compositions.

  such as hairspray, hair setting lotions,

  treatments, shampoos, color shampoos

  tinting compositions for hair, by means of

  such as nail polish, treatment creams for the treatment of

  dermis, foundations, lipstick sticks, as well as any other cosmetic composition that may present because of its constituents

  light stability problems during storage.

  The subject of the invantion is also a method of protecting the epi-

  human dermis against UV rays consisting in applying to the skin at least one compound of formula (I) contained in a cosmetically acceptable medium and optionally combined with other agents absorbing UV-A and / or UV-B rays. The invention also relates to a method for protecting colored cosmetic compositions against UV-B rays consisting in incorporating into these

  compositions at least one compound of formula (I).

  The Applicant has further discovered in the course of his research that the 3-benzylidene camphor derivatives of formula (I) have an activity

  pharmacological interest in the field of topical and systemic

  of acne, psoriasis and other dermatoses or dermatological conditions.

  3S inflammatory and allergic, as well as antitumor activity.

  The subject of the invention is therefore also a pharmaceutical composition containing an effective amount of at least one compound of formula (I)

  of active ingredient in a non-toxic carrier or excipient.

  Such a composition can be used in the topical and systemic treatment of benign or malignant neoplasias, premalignant lesions as well as

  only in the systemic and topical prophylaxis of these affections. It is

  Also comes in the treatment of dermatoses such as acne or psoriasis. It can also be used orally to treat certain rheumatic conditions such as, for example, rheumatism.

chronic.

  The compounds of formula (I) are generally administered orally at a daily dose of about 2 g to 5 mg per kg and preferably 10 ng

at 2 mg per kg.

  The topically compositions preferably contain from 0.0005% to about 5% by weight of compound of formula (I).

  As carrier or excipient of the pharmaceutical composition of the invention,

  tion, any conventional non-toxic carriers or excipients

  active compound either in the soluble state or in the

scattered in the support.

  The invention is illustrated by the nonlimiting examples of application below.

EXAMPLES OF FORMULATION

Example 5

  Protective Day Cream - Compound of Example 1 1, gs - 4'-methoxy-4-tert-butyl dibenzoylmethane sold under the name PARSOL 1789 by Givaudan 0.5 g - Sipol wax 7 g - Glycerol monostearate 2 g Vaseline oil 15 g - Silicone oil 1,5 g - Cetyl alcohol 1,5 g - Glycerine 10 g - Preservative, perfume qs - Water qs 100 g

Example 6

  Protective Day Cream - Compound of Example 3 0.3 g - 4-isopropyl dibenzoylmethane sold under the name EUSOLEX 8020 by MERCK 0.6 g Benzylidene camphor 0.5 g - C8 fatty acid triglycerides - C12 31 g Glycerol monostearate 6 g - Stearic acid 2 g - Cetyl alcohol 1, 2 g - Lanolin 4 g - Propanediol 2 g - Triethanolamine 0.5 g

- Preservative, perfume q.s.

  - water q.s. 100 g The creams of Examples 5 and 6 are prepared by heating the bodies

  fat around 80-85 C; we then add the (or) filter (s).

  In addition, the water and the water-soluble components are heated to

  80-85 C and with vigorous stirring, the fatty phase is added to the aqueous phase.

  Stirring is maintained for 10 to 15 minutes and allowed to cool under

moderate agitation.

Example 7

  Anti-solar protective milk - Sipol wax 5g - Vaseline oil 6g Isopropyl myristate 3g - Dimethylpolysiloxane 1g - Cetyl alcohol 1g - Glycerin 20g - Compound of Example 2 2g (as sodium salt ) - p-methyl benzylidene camphor 2 g - Water qs 100 g The compound of Example 2 is dissolved in water and glycerin. PMethylbenzylidene camphor is dissolved in the fatty phase and this milk is

  prepared according to the usual techniques for obtaining an O / W emulsion.

Example 8

  Sunscreen protective cream - Compound of Example 4 2 g

  4-C (2-oxo-3-bornylidene) methyl sulfate

  methylphenyl trimethylammonium 2,5 g - 2-hydroxy-4'-tert.butyl dibenzoylmethane prepared according to Example 1 of the French patent application 2,506,156 1 g - Polyoxyethylenated fatty alcohols 7 g - Triglycerides of fatty acids 30 g C8 - C12 - Glycerol monostearate 2 g - Silicone oil 1,5g - Cetyl alcohol 1,5 g

* - Preservative, perfume q.s.

  - Water q.s. 100 g The preparation of this cream is similar to that of Examples 5 and 6, the compound of Example 4 and 2-hydroxy-4'-tert-butyl dibenzoylmethane

  being dissolved in the fatty phase, 4-J2-oxo-3-norbornyl methylsulphate

  dane) methylphenyl trimethylammonium being dissolved in the aqueous phase.

Example 9

  Oily sunscreen lotion - Compound of Example 1 3 g - octyl pimethylamino benzoate 2 g - Cocoa butter 2.5 g

- Preservative, perfume q.s.

  - Triglycerides of C8 C12 fatty acids q.s. 100 g

  Heat to 40-45 C to homogenize the composition.

2o

Claims (18)

  1. Derivative of 3-benzylidene camphor of formula: o W> "R I (I)   R 1 in which R denotes a hydrogen atom, a methyl or ethyl radical, R 'denotes a hydrogen atom, a methyl or ethyl radical, Ret R' can not simultaneously designate a hydrogen atom, R1 denotes a group - C00R2, -CONHR2, -CO, -CHO, -CH (OR4) 2 or -CH20R4,   R2 being an alkyl, alkenyl, cycloalkyl or aralkyl radical containing at most 20 carbon atoms, optionally substituted by hydroxy, alkoxy, amine or quaternary ammonium groups, M denoting a hydrogen atom, an alkali metal or a group <(R 3 ) 4, R 3 being a hydrogen atom or a C 1 -C 4 alkyl or hydroxyalkyl radical R denoting a hydrogen atom or an alkyl, cycloalkyl or   aralkyl containing at most 20 carbon atoms.   2. Compound according to claim 1, characterized in that R and R '   do not simultaneously denote a methyl or ethyl radical.   3. Compound according to claim 1, of formula: O H3C l R   in which R1 denotes the radical: -C00C2H5, -C00E or -CONHC2R 05.   4. Compound according to claim 1, of formula: CH3 s COH5   5. Process for the preparation of a compound of formula (1) according to the   in which R is a hydrogen atom and R 'denotes a methyl or ethyl radical, characterized in that - in a first step is carried out a compound of formula: CH2 R '   bromination in inert solvent medium, to obtain the compound of formula: CH   Br R '- in a second step the brominated derivative is hydrolyzed with sodium hydroxide to obtain the secondary alcohol of formula: S t. HH HO R '   in a third step, the secondary alcohol above is oxidized to form a ketone of formula:   in a fourth step, the ketone above is subjected to   densing Wittig-Horner with a phosphonate of formula: (alkyl-O) 2 CH2COOR2 o alkyl preferably denotes methyl or ethyl, to obtain the compound of formula (I) wherein R is a hydrogen atom,   R 'is methyl or ethyl and R1 is -COOR2.   6. Process for the preparation of a compound of formula (I) according to claim   cation 1, wherein R denotes a methyl or ethyl radical and R 'is a hydrogen atom, characterized in that: HO DH Q Where   H SZ: nmuuo; ap aiTeuç.d iooaiei jluazqo inod ZuessTnd anazunp unp ap eTl e azuT zuvAlos naITm ua snssap-To   asodmoD np & xooeqiea adnog ael Fnpz uo 'adel apuo-as aun 8uep - aTxr-The-q 0 = D OZ   I SL: lnumol ap asodmoa el aiuazqo mnod alúq4p no alúltlm avUez OL -gjgid ap augTsap alCXle no al81e-O- to z (O-8 / -): alnmuo ap aezuoqdsoqd a DaAe xauaOH-2iTkl ap uotesuepuoz aun   : alnu.o; ap asodmoo ne ixqns wve; uo ade; p aeuTmaxd au su suep - 24 2556717   in a third step, the above primary alcohol is oxidized to the aldehyde of formula: X   In a fourth step, the above aldehyde is subjected to a Wittig-Horner condensation with a phosphonate of formula: (alkyl-O) 2 PCH 2 COOR 2, where alkyl denotes preferably methyl or   ethyl, to obtain the compound of formula (I) in which R denotes   thyl or ethyl, R 'is a hydrogen atom and R1 is -COOR2.   7. Process for the preparation of compounds of formula (I) according to the claim   in which R1 denotes a group -CO or -COHR2, M and R2 having the meanings indicated in claim 1, characterized in that saponifies the compounds of formula (I) in which R1 denotes -C00R2 prepared according to claim 5 or 6 to convert them to corresponding acids in which R1 is -COOH, the acids may then be salified with an alkaline base or an amine to yield compounds of formula (I) wherein R1 is COO0, MN being an alkaline ion or a group N (R3) 4, or the acids that can be converted into chlorides   of acids which are then reacted with an amine to form the corresponding amide.   of formula (I) in which R1 denotes -CONHR2.   8. Process for preparing a compound of formula (I) according to the claim   1 in which RI denotes a group -COOH, -CH (OR4) 2 or -C2OR4, R4 having the meaning indicated in claim 1, characterized in that the esters of formula (I) in which R1 is -COOR2 2556717   prepared according to claim 5 or 6 to convert them into alcohols of formula (I) in which R1 denotes -CH20H, then: - the alcohols are oxidized to obtain the corresponding aldehydes of formula (I) in which R1 denotes -CH0, on which alkanols, cycloalkanols or aralkyl alcohols may be added in an acidic medium to obtain the acetals of formula (I) in which R 1 denotes -CH (OR 4) 2 or the alcohols of formula (1) in which R 1 denotes -CH 2 OH with aldehydes in an acid medium to obtain the corresponding acetals of formula (I) in which R 1 denotes -CH (OR 4) 2 - or the alcohols of formula (I) in which R 1 denotes -CH 2 OH with a alkyl, cycloalkyl or aralkyl halide for   obtain the ethers of formula (I) in which R1 denotes -CH2OR4.   9. Cosmetic composition characterized in that it contains as an agent for protection against UV-B rays, an effective amount of   minus a 3-benzylidene camphor derivative of formula (I) according to the   1, in a cosmetically acceptable medium.   10. Cosmetic composition according to claim 9, characterized in that it contains as protection agent against UV-B rays, an effective amount of at least one compound of formula (I) as defined in the   claim 2 in a cosmetically acceptable medium.   11. Cosmetic composition according to claim 9 or 10, carctérisée in that the compound of formula (I) is present in proportions   between 0.5 and 15% by weight relative to the total weight of the composition tion.   12. Cosmetic composition according to any one of claims 9 to   11, characterized in that it contains at least one cosmetic adjuvant chosen from thickeners, softeners, superfatting agents,   emollients, humectants, wetting agents, surfactants, preservatives   anti-foams, perfumes, oils, waxes, dyes and / or the pigments.   13. Cosmetic composition according to any one of claims 9 to   12, in the form of an anti-solar composition, characterized in that it contains at least one compound of formula (I) combined with other water-soluble or fat-soluble sunscreens having a filtering action with respect to the rays. UV-B such as camphor derivatives, coffee oil, 26 2556717   salicylic acid derivatives, cinnamic acid derivatives, p-aminobenzoic acid derivatives, benzophenone derivatives, or other UV-A filtering sunscreens such as dibenzoylmethane derivatives .   14. Cosmetic composition according to any one of claims 9   at 12 in the form of a protective day cream, characterized in that it contains at least one compound of formula (I) associated with the   minus a UV-A filter such as a dibenzoylmethane derivative.   15. Cosmetic composition according to any one of claims 9 to   12, in the form of a colored cosmetic composition or not, stabilized with light, characterized in that it is constituted by a hair composition such as a hair lacquer, a lotion of   styling, a shampoo, a coloring shampoo, a tincture composition,   a hair makeup product, such as a nail polish, a lipstick stick, a skin cream or a foundation. 16. Method of protecting the human epidermis against UV-B rays   characterized by applying to the skin in an effective amount   at least one compound of the formula (I) defined in claim 1,   contained in a cosmetically acceptable medium.   17. A method of protecting a colored cosmetic composition against UV-B rays, characterized in that it incorporates to this composition an effective amount of at least one compound of formula (I) defined in FIG. claim 1.   18. Pharmaceutical composition characterized by containing   an effective amount of at least one compound of formula (I) according   cation 1 in a non-toxic carrier or excipient.